全文获取类型
收费全文 | 886篇 |
免费 | 62篇 |
出版年
2022年 | 5篇 |
2021年 | 9篇 |
2020年 | 5篇 |
2019年 | 6篇 |
2018年 | 15篇 |
2017年 | 7篇 |
2016年 | 18篇 |
2015年 | 13篇 |
2014年 | 23篇 |
2013年 | 40篇 |
2012年 | 31篇 |
2011年 | 47篇 |
2010年 | 24篇 |
2009年 | 19篇 |
2008年 | 40篇 |
2007年 | 33篇 |
2006年 | 46篇 |
2005年 | 25篇 |
2004年 | 38篇 |
2003年 | 27篇 |
2002年 | 40篇 |
2001年 | 29篇 |
2000年 | 20篇 |
1999年 | 30篇 |
1998年 | 20篇 |
1997年 | 11篇 |
1996年 | 13篇 |
1995年 | 14篇 |
1994年 | 13篇 |
1993年 | 11篇 |
1992年 | 23篇 |
1991年 | 28篇 |
1990年 | 19篇 |
1989年 | 24篇 |
1988年 | 15篇 |
1987年 | 17篇 |
1986年 | 22篇 |
1985年 | 10篇 |
1984年 | 14篇 |
1983年 | 11篇 |
1982年 | 14篇 |
1981年 | 7篇 |
1979年 | 13篇 |
1978年 | 6篇 |
1976年 | 6篇 |
1974年 | 7篇 |
1973年 | 7篇 |
1971年 | 4篇 |
1969年 | 5篇 |
1968年 | 5篇 |
排序方式: 共有948条查询结果,搜索用时 250 毫秒
51.
The alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) enhanced the levels of plasminogen activator (PA) activity in fibroblast cells derived from the skin of patients with tuberous sclerosis. The enhanced enzyme levels were not correlated with those of cloning efficiency nor those of DNA synthesis after MNNG treatment. Enzyme enhancement was also observed in fibroblasts of ataxia telangiectasia and in human neoplastic glia cells, but not in fibroblasts of normal children. The PA induction test may be sufficiently sensitive for the detection of the cellular defects of tuberous sclerosis. 相似文献
52.
Toru Sugita Yukari Semi Hiromasa Sawada Yumi Utoyama Yuko Hosomi Eri Yoshimoto Yuki Maehata Hiroyuki Fukuoka Ryutaro Nagata Akio Ohyama 《Molecular breeding : new strategies in plant improvement》2013,31(4):909-920
To facilitate marker-assisted breeding and genetic analyses of pepper (Capsicum annuum), we developed non-redundant 2- or 3-base simple sequence repeat (SSR) markers from enriched C. annuum genomic libraries and from C. annuum cDNA sequences in public databases. The SSR-enriched libraries were constructed using combinations of three restriction enzymes (AluI, HaeIII, and RsaI) and two biotinylated oligonucleotides [b(GA)15 and b(CA)15]. Ultimately, we obtained 1,736 genomic SSR markers and 1,344 cDNA-derived SSR markers from 6,528 clones and 13,003 sequences, respectively. We mapped 597 markers, including 265 of the newly developed SSR markers, onto a linkage map by using doubled-haploid (DH) lines derived from an intraspecific cross of two pure lines of C. annuum (K9-11 × MZC-180). The map, designated as the KL-DH map, consisted of 12 linkage groups. The map covered a genetic distance of 2,028 cM, and the average distance between markers was less than 4 cM. The frame structure of the KL-DH map was compared with the published standard conserved ortholog set II (COSII) map, which was derived from an interspecific F2 population (C. frutescens × C. annuum), by using tomato (Solanum lycopersicum) chromosomal sequences to bridge the two maps. The intraspecific KL-DH map constructed in this study and the interspecific COSII map were similar in map length and marker distribution, suggesting that the KL-DH map covers nearly the whole genome of C. annuum. 相似文献
53.
54.
55.
Keisuke Maruyama Masaharu Nakamura Shusuke Tomoshige Kazuyuki Sugita Makoto Makishima Yuichi Hashimoto Minoru Ishikawa 《Bioorganic & medicinal chemistry letters》2013,23(14):4031-4036
Our multi-template approach for drug discovery, focusing on protein targets with similar fold structures, has yielded lead compounds for various targets. We have also shown that a diphenylmethane skeleton can serve as a surrogate for a steroid skeleton. Here, on the basis of those ideas, we hypothesized that the diphenylmethane derivative bisphenol A (BPA) would bind to the ligand-binding domain of estrogen receptors (ERs) in a similar manner to estradiol and act as a steroid surrogate. To test this idea, we synthesized a series of BPA analogs and evaluated their structure-activity relationships, focusing on agonistic/antagonistic activities at ERs and ERα/ERβ subtype selectivity. Among the compounds examined, 18 was found to be a potent ERα-antagonist with high selectivity over ERβ and androgen receptor under our assay conditions. A computational docking study suggested that 18 would bind to the antagonistic conformation of ERα. ERα-selective antagonists, such as 18, are candidate agents for treatment of breast cancer. 相似文献
56.
Chie Hashimoto Tetsuo Narumi Hiroyuki Otsuki Yuki Hirota Hiroshi Arai Kazuhisa Yoshimura Shigeyoshi Harada Nami Ohashi Wataru Nomura Tomoyuki Miura Tatsuhiko Igarashi Shuzo Matsushita Hirokazu Tamamura 《Bioorganic & medicinal chemistry》2013,21(24):7884-7889
To date, several small molecules of CD4 mimics, which can suppress competitively the interaction between an HIV-1 envelope glycoprotein gp120 and a cellular surface protein CD4, have been reported as viral entry inhibitors. A lead compound 2 (YYA-021) with relatively high potency and low cytotoxicity has been identified previously by SAR studies. In the present study, the pharmacokinetics of the intravenous administration of compound 2 in rats and rhesus macaques is reported. The half-lives of compound 2 in blood in rats and rhesus macaques suggest that compound 2 shows wide tissue distribution and relatively high distribution volumes. A few hours after the injection, both plasma concentrations of compound 2 maintained micromolar levels, indicating it might have promise for intravenous administration when used combinatorially with anti-gp120 monoclonal antibodies. 相似文献
57.
Yuji Nakamura Teppei Fujimoto Yasuyuki Ogawa Hidenori Namiki Sayaka Suzuki Masayoshi Asano Chie Sugita Akiyoshi Mochizuki Shojiro Miyazaki Kazuhiko Tamaki Yoko Nagai Shin-ichi Inoue Takahiro Nagayama Mikio Kato Katsuyoshi Chiba Kiyoshi Takasuna Takahide Nishi 《Bioorganic & medicinal chemistry》2013,21(11):3175-3196
With the aim to address an undesired cardiac issue observed with our related compound in the recently disclosed novel series of renin inhibitors, further chemical modifications of this series were performed. Extensive structure–activity relationships studies as well as in vivo cardiac studies using the electrophysiology rat model led to the discovery of clinical candidate trans-adamantan-1-ol analogue 56 (DS-8108b) as a potent renin inhibitor with reduced potential cardiac risk. Oral administration of single doses of 3 and 10 mg/kg of 56 in cynomolgus monkeys pre-treated with furosemide led to significant reduction of mean arterial blood pressure for more than 12 h. 相似文献
58.
Tomohisa Nagasaki Masanori Sugita Hideaki Fukawa Hsin-Tung Lin 《Bioscience, biotechnology, and biochemistry》2013,77(2):363-369
Taxonomical investigation was performed on the bacterium, strain NB 320 isolated from soil, and it was identified as Enterobacter cloacae. This bacterium produced the enzyme which catalyzed the transamination reaction between 3,4-dihydroxyphenyl pyruvate and an amino acid to form l-Dopa.The optimum culture conditions for the enzyme production were studied along with the characteristics of the enzyme. The enzyme of the strain was different in some properties from that of Alcaligenes faecalis IAM 1015 which had been already studied. The former utilized glutamate as an amino donor best among the amino acids tested for transamination and was induced by the addition of glutamine and asparagine. Intact cells of the strain did not catalyze the reaction unless they were treated with sonication or with a detergent. 相似文献
59.
Tomohisa Nagasaki Masanori Sugita Hideaki Fukawa 《Bioscience, biotechnology, and biochemistry》2013,77(7):1701-1706
Some enzymatic properties were examined on the transaminase (DOPA transaminase) which catalyzes the reaction between 3,4-dihydroxy phenyl pyruvate (DOPP) and certain amino acids to form 3,4-dihydroxyphenyl-L-alanine (DOPA). The cell-free extract from Alcaligenes faecalis IAM 1015 was used as the DOPA transaminase. L-Aspartate, L-glutamate, and L-phenylalanine were utilized efficiently as amino donor. The occurrence of three kinds of transaminase—aspartate-DOPP transaminase (ADT), glutamate-DOPP transaminase (GDT), and phenylalanine-DOPP transaminase (PDT)—was postulated.The pH optima of these enzymes were observed in the alkaline pH range. The enzymes were unstable in the acidic range and inactivated above 60°C. Ca2+, Mg2+, and Mn2+ protected PDT from heat denaturation. Fe2+, Cu2+, and Al3+ remarkably inhibited the enzyme reaction. 相似文献
60.
Yasuo Noda Yoshiki Ida Shinichi Tanaka Taku Toyama Murilo Felix Roggia Yasuhiro Tamaki Naohiko Sugita Mamoru Mitsuishi Takashi Ueta 《PloS one》2013,8(1)